Prednisolone irreversibly binds with glucocorticoid receptors (GR) alpha and beta for which they have a high affinity. AlphaGR and BetaGR are found in virtually all tissues with variable numbers between 3000 and 10000 per cell, depending on the tissue involved. Prednisolone can activate and influence biochemical behaviour of most cells. The steroid/receptor complexes dimerise and interact with cellular DNA in the nucleus, binding to steroid-response elements and modifying gene transcription. They induce synthesis of some proteins, and inhibit synthesis of others.[7][8]

Not all metabolic actions on genes are known. Most mediator proteins are enzymes, e.g., cAMP-dependent kinase

Regulation of gene suppression leads to systemic suppression of inflammation and immune response. This is of clinical usefulness but ultimately leads to gluconeogenesis, proteolysis and lipolysis. Gene transcription returns to normal after cessation, but sudden stoppage can cause Addison's disease. Osteoporosis is permanent.

A lengthy course of prednisolone can cause bloody or black tarry stools from bleeding into the stomach (this requires urgent medical attention); filling or rounding out of the face; muscle cramps or pain; muscle weakness; nausea; pain in back, hips, ribs, arms, shoulders, or legs; reddish-purple stretch marks on arms, face, legs, trunk, or groin; thin and shiny skin; unusual bruising; urinating at night; rapid weight gain; and wounds that will not heal.

Prolonged use of prednisolone can lead to the development of osteoporosis which makes bones more fragile and susceptible to fractures. One way to help alleviate this side effect is through the use of calcium and vitamin D supplements.[9]

having strange and frightening thoughts, changing behaviour or having feelings of being alone

Nasal septum perforation and bowel perforation are also notable adverse effects that restrict steroids' use in some pathologic conditions.[11][12]

Withdrawal from prednisolone can be problematic after taking large doses or over more than two weeks.[13] This is caused by prednisolone inhibiting the natural production of corticosteroids in the "Hypothalamic-Pituitary-Adrenal Axis" (HPAA)[13]

As a glucocorticosteroid, unauthorized or ad-hoc use of prednisolone during competition via oral, intravenous, intramuscular or rectal routes is banned under WADA anti-doping rules.[14] The drug may be used in competition with a TUE (Therapeutic Use Exemption), in compliance with WADA regulations. Local or topical use of prednisolone during competition as well as any use out of competition is not regulated.